Immature muscle precursors are a source of interferon-β in myositis: role of Toll-like receptor 3 activation and contribution to HLA class I up-regulation

Arthritis Rheum. 2012 Feb;64(2):533-41. doi: 10.1002/art.33350.


Objective: To investigate the production of type I interferon (IFN) by myoblasts and to identify its cell source and the link to Toll-like receptor (TLR) and C-type lectin receptor (CLR) expression and function in myositis biopsy sections.

Methods: Production of IFNβ was assessed in cultured myoblasts after stimulation with the TLR-3 agonist poly(I-C) or with cytokines involved in Th1 and Th17 differentiation. Expression of HLA class I molecules by myoblasts was analyzed by fluorescence-activated cell sorting after activation of TLR-3 and IFNβ neutralization. In muscle biopsy samples from patients with polymyositis or dermatomyositis, expression of IFNβ, CD56 (a marker of immature muscle precursors), and HLA class I was analyzed using immunohistochemistry. Inflammatory infiltrates were characterized for the expression of myeloid dendritic cells (DCs), their associated CLRs, and the products of activated DCs, interleukin-12 (IL-12), and IL-23.

Results: In cultured myoblasts, stimulation of TLR-3 induced the production of IFNβ when combined with IFNγ and up-regulated the expression of HLA class I molecules, which was decreased after IFNβ blockade. In myositis biopsy tissues, immature muscle precursors overexpressing HLA class I were identified as a source of IFNβ. CLRs associated with myeloid DCs were broadly expressed in inflammatory infiltrates, in association with IL-12 and IL-23, and with immature muscle precursors.

Conclusion: Immature muscle precursors may represent a local source of IFNβ and the target of an immune response involving activated DCs associated with the expression of CLRs and of IL-12 and IL-23, which are implicated in T cell polarization. In turn, such local production of IFNβ after TLR-3 activation in the presence of the Th1 cytokine IFNγ may explain HLA class I overexpression in myositis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cells, Cultured
  • Dermatomyositis / metabolism*
  • Female
  • Genes, MHC Class I / physiology*
  • Humans
  • Interferon-beta / metabolism*
  • Male
  • Middle Aged
  • Myoblasts / metabolism*
  • Osteoarthritis / metabolism
  • Polymyositis / metabolism*
  • Toll-Like Receptor 3 / metabolism*
  • Up-Regulation


  • Toll-Like Receptor 3
  • Interferon-beta